Black women suffer more early, aggressive, lethal breast cancers than do White women of Northern European ancestry. While Blacks of African ancestry may have a higher frequency of cancer promoting genes, e.g. BRCA 1 mutations, this dramatic health disparity may also have psychosocial origins. Our animal model demonstrating larger mammary carcinomas in socially isolated and hypervigilant rats enables us to identify specific mechanisms of ovarian and adrenal function that increase the penetrance of mammary cancer promoting genes. Group-living female rats typically develop mammary tumors in late adulthood, in a logarithmic pattern similar to breast cancer dynamics in White women of Northern European ancestry. In stark contrast, socially isolated and hypervigilant rats, with the same genome, develop mammary cancers 40% younger, at 4 times the rate and have larger and more aggressive tumors, similar to breast cancer dynamics in Blacks of African ancestry. Our distinctive animal model permits study of tumor development against the backdrop of normal endocrine function. Because puberty is a sensitive period, we will study characteristics of pubertal ovarian function in socially isolated and group living rats that predict different dynamic patterns of spontaneous ovarian cycles and life-long exposure to estrogen and progesterone. Finally, we will determine how social isolation and hypervigilance alter the timing of mammary gland development relative to ovarian function and pregnancy, increasing sensitivity to carcinogens. In this project we will compare the mammary tumors of socially isolated and group-living rats to determine if both spontaneous and carcinogen-induced (7,12-dimethylbenz(a)anthracene, DMBA) tumors in the two psychosocial conditions are (1) morphologically different (2) have different expression of estrogen and progesterone receptors, and (3) have somatic alterations of rat genes Brcal, ErbB-2/Neu, or c-myc, whose homologs are known to be dysfunctional in Black women with early breast cancer. We will create a tissue bank from all tumors collected in these experiments enabling future collaborative studies by investigators using both proteomic and functional genomic approaches to test additional hypotheses generated by this and other Centers. Insights from this animal model will inform a test of the hypothesis that hypervigilance and social isolation in Black women of African ancestry increase their risk of early, lethal breast cancers.